Higher peripheral blood mitochondrial DNA copy number and relative telomere length in under 48 years Indonesian breast cancer patients.

OBJECTIVE: Breast cancer is the leading cause of cancer incidence and mortality among Indonesian women. A comprehensive investigation is required to enhance the early detection of this disease. Mitochondrial DNA copy number (mtDNA-CN) and relative telomere length (RTL) have been proposed as potential biomarkers for several cancer risks, as they are linked through oxidative stress mechanisms. We conducted a case-control study to examine peripheral blood mtDNA-CN and RTL patterns in Indonesian breast cancer patients (n = 175) and healthy individuals (n = 181). The relative ratios of mtDNA-CN and RTL were determined using quantitative real-time PCR (qPCR). RESULTS: Median values of mtDNA-CN and RTL were 1.62 and 0.70 in healthy subjects and 1.79 and 0.73 in breast cancer patients, respectively. We found a positive association between peripheral blood mtDNA-CN and RTL (p < 0.001). In under 48 years old breast cancer patients, higher peripheral blood mtDNA-CN (mtDNA-CN ≥ 1.73 (median), p = 0.009) and RTL (continuous variable, p = 0.010) were observed, compared to the corresponding healthy subjects. We also found a significantly higher 'High-High' pattern of mtDNA-CN and RTL in breast cancer patients under 48 years old (p = 0.011). Our findings suggest that peripheral blood mtDNA-CN and RTL could serve as additional minimally invasive biomarkers for breast cancer risk evaluation.

Prognostic Values of CD8+, PARP, and EGFR on Overall Survival in Patients with Triple-Negative Breast Cancer.

OBJECTIVE: This study aimed to investigate the associations of CD8+, PARP, and EGFR expressions with two-year survival in patients with triple-negative breast cancer (TNBC). METHODS: A retrospective cohort study was conducted in a national cancer center. All patients aged 18 years diagnosed with TNBC (2013-2017) were included and followed for 24 months or until the patients were deceased. Kaplan-Meier survival function and Cox proportional hazard model were applied for the analyses. RESULTS: The study population was followed for 24 months (2,692 person-months, N = 126). At the end of the follow-up, 27 patients were deceased. The two-year mortality rate was 10 per 1,000 person-month. Kaplan-Meier graphs showed that after approximately one year of follow-up, poorer survival was seen in patients with low CD8+, positive PARP, and positive EGFR. The adjusted analysis found staging as the main predictor of overall survival in TNBC (HR = 7.20, 95% CI= 2.07 - 25.00). CONCLUSIONS: Patients with low CD8+, positive PARP, and positive EGFR expressions seem to be associated with poorer overall survival in TNBC. After approximately one year of follow-up, higher survival was observed in patients with high CD8+, negative PARP, and negative EGFR. Staging remains the main predictor of TNBC survival. Therefore, early detection and treatment of TNBC are essential to improve survival.

The relationship between high ratios of CD4/FOXP3 and CD8/CD163 and the improved survivability of metastatic triple-negative breast cancer patients: a multicenter cohort study.

BACKGROUND: Triple-negative breast cancer (TNBC) has been documented as the most aggressive subtype of breast cancer. This study aimed to analyze antitumor and protumor immune activities, and their ratios as significant prognostic biomarkers in metastatic TNBC (mTNBC). METHODS: A multicenter cohort study was conducted among 103 de novo mTNBC patients. The expression of CD8 and CD163 was evaluated using immunohistochemistry staining, CD4 and FOXP3 using double-staining immunohistochemistry, and PD-L1 using immunohistochemistry and RT-PCR. RESULTS: Multivariate analysis revealed that high CD4/FOXP3 (HR 1.857; 95% CI 1.049-3.288; p = 0.034) and the CD8/CD163 ratio (HR 2.089; 95% CI 1.174-3.717; p = 0.012) yield significantly improved 1 year overall survival (OS). Kaplan-Meier analysis showed that high levels of CD4 (p = 0.023), CD8 (p = 0.043), CD4/FOXP3 (p = 0.016), CD8/FOXP3 (p = 0.005), CD8/CD163 (p = 0.005) ratios were significantly associated with higher rate of 1 year OS. Furthermore, 1 year OS was directly correlated with antitumor CD4 (R = 0.233; p = 0.018) and CD8 (R = 0.219; p = 0.026) and was indirectly correlated with protumor CD163 and FOXP3 through CD4/FOXP3 (R = 0.282; p = 0.006), CD4/CD163 (R = 0.239; p = 0.015), CD8/FOXP3 (R = 0.260; p = 0.008), and CD8/CD163 (R = 0.258; p = 0.009). CONCLUSION: This is the first study to demonstrate that high levels of CD4/FOXP3 and CD8/CD163 significantly improved the 1 year OS in de novo mTNBC patients. Thus, we recommend the application of these markers as prognosis determination and individual treatment decision.

Genomic features of lung cancer patients in Indonesia's national cancer center.

INTRODUCTION: Advances in molecular biology bring advantages to lung cancer management. Moreover, high-throughput molecular tests are currently useful for revealing genetic variations among lung cancer patients. We investigated the genomics profile of the lung cancer patients at the National Cancer Centre of Indonesia. METHODS: A retrospective study enrolled 627 tissue biopsy samples using real time polymerase chain reaction (RT-PCR) and 80 circulating tumour DNA (ctDNA) liquid biopsy samples using next-generation sequencing (NGS) from lung cancer patients admitted to the Dharmais Cancer Hospital from January 2018 to December 2022. Data were obtained from medical records. Data statistically analysed with p < 0.05 is considered significant. RESULT: The EGFR test results revealed by RT-PCR were wild type (51.5%), single variant (38.8%), double variant (8.3%), and triple variant (1.4%), with 18.66% L85R, 18.22% Ex19del, and 11.08% L861Q variant. Liquid biopsy ctDNA using NGS showed only 2.5% EGFR wild type, 62.5% single variant and 35% co-variant, with EGFR/TP53 and EGFR/PIK3CA as the highest. CONCLUSION: EGFR variants are the most found in our centre. Liquid biopsy with ctDNA using NGS examination could detect broad variants and co-variants that will influence the treatment planning.

Circulating miR-10b, soluble urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 as predictors of non-small cell lung cancer progression and treatment response.

BACKGROUND: Despite advances in lung cancer treatment, most lung cancers are diagnosed at an advanced stage. Expression of microRNA10b (miR-10b) and fibrinolytic activity, as reflected by soluble urokinase-type plasminogen activator receptor (suPAR) and plasminogen activator inhibitor 1 (PAI-1), are promising biomarker candidates. OBJECTIVE: To assess the expression of miR-10b, and serum levels of suPAR and PAI-1 in advanced stage non-small cell lung cancer (NSCLC) patients, and their correlation with progression, treatment response and prognosis. METHODS: The present prospective cohort and survival study was conducted at Dharmais National Cancer Hospital and included advanced stage NSCLC patients diagnosed between March 2015 and September 2016. Expression of miR-10b was quantified using qRT-PCR. Levels of suPAR and PAI-1 were assayed using ELISA. Treatment response was evaluated using the RECIST 1.1 criteria. Patients were followed up until death or at least 1 year after treatment. RESULTS: Among the 40 patients enrolled, 25 completed at least four cycles of chemotherapy and 15 patients died during treatment. Absolute miR-10b expression ⩾ 592,145 copies/µL or miR-10b fold change ⩾ 0.066 were protective for progressive disease and poor treatment response, whereas suPAR levels ⩾ 4,237 pg/mL was a risk factor for progressive disease and poor response. PAI-1 levels > 4.6 ng/mL was a protective factor for poor response. Multivariate analysis revealed suPAR as an independent risk factor for progression (ORa⁢d⁢j, 13.265; 95% confidence intervals (CI), 2.26577.701; P= 0.006) and poor response (ORa⁢d⁢j, 15.609; 95% CI, 2.221-109.704; P= 0.006), whereas PAI-1 was an independent protective factor of poor response (ORa⁢d⁢j, 0.127; 95% CI, 0.019-0.843; P= 0.033). CONCLUSIONS: Since miR-10b cannot be used as an independent risk factor for NSCLC progression and treatment response, we developed a model to predict progression using suPAR levels and treatment response using suPAR and PAI-1 levels. Further studies are needed to validate this model.

Metabolic Profile and Negatively Association Between Insulin Resistance and Metastatic Incidence in Indonesian Primary Invasive Breast Cancer: A Cross-Sectional Study.

Introduction: Metastatic breast cancer was associated with high morbidity and mortality. Insulin resistance was hypothesized to be related to the incidence of advanced breast cancer. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Triglyceride/Glucose Index (TyG Index) are two metrics used to measure the degree of insulin resistance. This study aims to assess the relationship between the incidence of metastatic breast cancer and insulin resistance as reflected by both metrics. Material and Methods: This study is a cross-sectional study involving 150 primary invasive breast cancer patients recruited from two hospitals of different sectors from August 2019 to April 2020. Patients with double cancer and autoimmune disorder were excluded from this study. Data obtained from the patients include age, body mass index (BMI), type 2 diabetes mellitus (T2DM) status and treatment, and low-density lipoprotein (LDL) cholesterol. The electronic medical records (EMR) was consulted to find histopathology examination result, cancer staging, and any missing data. The association between HOMA-IR and TyG with metastatic incidence was analyzed using either the Mann-Whitney test (for non-normally distributed data) or the independent-sample t-test (for normally distributed data). Results: The mean of the TyG index is 8.60, and the median of HOMA-IR is 1.22. We found no significant correlation between both variables and the incidence of metastases. Conclusion: Insulin resistance was not associated with metastatic breast cancer.

Circulating miR-221/222 expression as microRNA biomarker predicting tamoxifen treatment outcome: a case-control study.

The high mortality rate in breast cancer (BC) patients is generally due to metastases resistant to systemic therapy. Two causes of systemic therapy resistance in BC patients are circulating miRNAs-221 and miR-222, leading to improved BC cell proliferation, survival, and reduced cell apoptosis. This study investigated the miRNA expression changes associated with cancer cell resistance to tamoxifen therapy and is expected to be clinically meaningful before providing endocrine therapy to luminal-type BC patients who express them. Methods: This case-control research included individuals with the luminal subtype of BC who had received tamoxifen medication for around one year. Furthermore, the case group contained 15 individuals with local recurrence or metastases, while the control group comprised 19 patients without local recurrence or metastases. Plasma miR-221/222 quantification was performed with real-time PCR using transcript-specific primers. Results: A significant difference was found in circulating miR-221 expression between cases and controls (P=0.005) but not in miR-222 expression (P=0.070). There were no significant differences between miR-221/222 expression, progesterone receptor, Ki67 protein levels, lymphovascular invasion, and stage. However, receiver operator characteristic curve analyses showed miR-221/222 expressions predictive of tamoxifen resistance (P=0.030) with a sensitivity of 60.00 and a specificity of 83.33%. Conclusion: The use of circulating miR-221/222 expression can predict relapse as well as resistance to tamoxifen treatment in BC patients, and their testing is recommended for luminal subtype BC patients who will undergo tamoxifen therapy to determine their risk of tamoxifen resistance early, increasing treatment effectiveness.

Association of Body Composition and Handgrip Strength with Interleukin-6 (IL-6) and Vitamin D Level in Cancer Patients.

Introduction: Cachexia is prevalent in cancer and is associated with poorer prognosis. We aimed to investigate the association of interleukin-6 (IL-6) and vitamin D levels with cachexia in cancer patients. We also assessed the relationship between body composition profile and cachexia, IL-6, and vitamin D levels. Methods: A cross-sectional study was conducted at Dharmais National Cancer Hospital. The study included patients with newly diagnosed biopsy-proven nasopharyngeal cancer, lung cancer, breast cancer, cervical cancer, or non-Hodgkin lymphoma. Blood samples, anthropometrics, and body composition were measured. Results: A total of 150 cancer patients were included in the study, with a median age of 52 years, and 64% (n = 96) are female. The prevalence of cachexia was 57%. Cancer patients with cachexia had higher IL-6 levels (P = 0.025). No association between cachexia and vitamin D levels was found (P = 0.787). Patients with cachexia had lower body composition components than those without cachexia (P < 0.05). Vitamin D levels were positively correlated with muscle mass, visceral fat, and handgrip strength (P < 0.05), while no association between IL-6 and body composition was found. Conclusion: Cancer-associated cachexia is associated with a higher level of IL-6, lower BMI, lower fat mass index, and lower visceral fat. Vitamin D levels, but not IL-6, are correlated with muscle mass, muscle strength, and visceral fat in cancer patients.

Overweight and Obesity are Associated with Poorer Survival Among Patients with Advanced Non-Small Cell Lung Cancer Receiving Platinum-Based Chemotherapy.

Background and Aim: Most patients with non-small cell lung cancer (NSCLC) are diagnosed in advanced-stage disease and therefore have poor overall survival. It remains unclear whether nutritional status affects response rate and overall survival in NSCLC patients. This study aimed to evaluate the association of nutritional status with treatment response and overall survival in patients with advanced stage of NSCLC. Methods: Patients aged ≥18 years with stage II-IV NSCLC (January-June 2018) in a national cancer center in Indonesia were enrolled in this study. The patients were followed up for 2 years since NSCLC diagnosis was established. Clinical data including age, sex, histology of cancer, disease stage, cachexia, and weight status before chemotherapy were reviewed and analyzed. Logistic regression and Cox regression analyses were performed. Results: A total of 174 patients (71% males, mean age = 58±9.4 years) was included. Complete response was found in <1% patients, partial response 41%, stable disease 33%, and progressive disease 25%. Median survival was 12 months (95% CI: 11-13 months). Mortality rate was 5.7 per 100 person-months. Poor survival was associated with being males (HR: 1.77, 95% CI: 1.15-2.72, P = 0.009), and overweight or obesity (HR 1.67, 95% CI: 1.04-2.69, P = 0.034). These associations were independent of sex, age, staging, histopathology, performance status and D-dimer level at baseline. Cachexia and BMI at baseline were not associated with treatment response. Conclusion: Males and having overweight or obesity are independently associated with lower survival in patients with advanced stage of NSCLC undergoing platinum-based chemotherapy.

Pretreatment nutritional status, HPV infection, and tumor infiltrating lymphocyte as prognostic predictors in patients with head and neck squamous cell carcinoma after chemotherapy.

Background: The survival rate in head and neck cancer varies among the subtypes, yet, the factors associated with survival between studies are still conflicting. This study aimed to investigate the association between pretreatment nutritional status, human papilloma virus (HPV) infection, tumor infiltrating lymphocyte (TIL), and treatment response after chemotherapy in patients with head and neck squamous cell carcinoma (HNSCC) in Indonesia. Further, factors associated with overall survival were also assessed. Methods: This was a retrospective cohort study. Data were collected between January 2015 and January 2018. A total of 30 patients with histopathologically proven squamous cell carcinoma head and neck cancer who had received at least three cycles of chemotherapy were included. Nutritional status was assessed using body mass index (BMI). Results: The mean BMI was 21.8 kg/m2 (Standard Deviation 3.98). The underweight patients had a higher risk of progressive disease (OR = 12.1, 95% CI = 1.1-135.6, P = 0.04) compared to patients with higher BMI. Neither HPV infection nor TIL was associated with treatment response and overall survival (P > 0.05). The median survival for the underweight patients was 9 months (95% CI = 3.00-15.00), whereas the median survival for normal and obese patients was 14 months (95% CI = 9.33-18.67). Conclusion: Underweight is associated with a significantly higher risk of progressive disease and tends to have shorter overall survival in patients with HNSCC. Yet, neither HPV infection nor TIL was associated with treatment response and overall survival.

Advance care planning for patients with cancer and family caregivers in Indonesia: a qualitative study.

BACKGROUND: Individuals' willingness to engage in advance care planning is influenced by factors such as culture and religious beliefs. While most studies on advance care planning in Asia have been performed in high-income countries, Indonesia is a lower-middle-income country, with a majority of strongly collectivist and religiously devout inhabitants. We studied the perspectives of Indonesian patients with cancer and family caregivers regarding advance care planning by first exploring their experiences with medical information-disclosure, decision-making, and advance care planning and how these experiences influence their perspectives on advance care planning. METHODS: We conducted semi-structured interviews among 16 patients with cancer and 15 family caregivers in a national cancer center in Jakarta and a tertiary academic general hospital in Yogyakarta. We performed an inductive thematic analysis using open, axial, and selective coding. The rigor of the study was enhanced by reflective journaling, dual coding, and investigator triangulation. RESULTS: Twenty-six of 31 participants were younger than 60 years old, 20 were Muslim and Javanese, and 17 were college or university graduates. Four major themes emerged as important in advance care planning: (1) participants' perceptions on the importance or harmfulness of cancer-related information, (2) the importance of communicating bad news sensitively (through empathetic, implicit, and mediated communication), (3) participants' motives for participating in medical decision-making (decision-making seen as patients' right or responsibility, or patients' state of dependency on others), and (4) the complexities of future planning (e.g., due to its irrelevance to participants' religious beliefs and/or their difficulties in seeing the relevance of future planning). CONCLUSIONS: Culturally sensitive approaches to advance care planning in Indonesia should address the importance of facilitating open communication between patients and their families, and the various perspectives on information provision, bad news communication, and decision-making. Advance care planning should focus on the exploration of patients' values, rather than drafting treatment plans in advance.

Clinical Laboratory Results as Prognosis Marker in Advanced Stage Non-small Cell Lung Cancer (NSCLC) in Indonesia.

BACKGROUND: Lung cancer is the most common cause of cancer-related death among men in the world. Given the very high mortality caused by lung cancer, a biological marker to determine a more sensitive therapy among non-small cell lung cancer (NSCLC) patients is needed. This study aims to demonstrate that the clinical laboratory result can be a prognosis marker in NSCLC patients in Indonesia. METHODS: This study was a retrospective cohort study. The sample was obtained from the patient's serum and the examined routine blood test (hemoglobin, leukocyte, platelets), hemostasis (fibrinogen and D-dimers), blood chemistry test (aspartate transaminase [AST], alanine transaminase [ALT], albumin, urea, creatinine, and blood glucose), electrolyte (sodium, potassium, chloride, and calcium) and tumor markers (carcinoembryonic antigen [CEA] and Cyfra 21-1). Data were analyzed and interpreted using SPSS (IBM Corp., Armonk, NY, USA). Analysis of the data was done to find the survival rate of sociodemographic variables, clinicopathologic variables, and clinic laboratory variables. RESULTS: The study findings showed statistically significant results that were poor prognosis for these following conditions: performance status (PS) 3-4 median survival (MS):26 days, p=<0.001; TNM stage IVb MS:58 days, p=0.001; high leukocyte MS:69 days, p=0.018; low platelet MS:50 days, p=0.013; high D-dimer MS:69 days, p=0.020; low albumin MS:56 days, p=0.001; high sodium MS:15 days, low sodium MS:50 days, p=<0.001; high chloride MS:15 days, low chloride MS:27 days, p=<0.001. CONCLUSION: In the advanced stage NSCLC, these findings indicate poorer prognoses; PS 3-4, IVb clinical stage, leukocytosis, thrombocytopenia, hyper-coagulopathy, hypoalbuminemia, hyper-hyponatremia, and hyper-hypochloremia. Further studies regarding the correlation between clinical laboratory and survival rate are needed.

Opportunities and challenges for advance care planning in strongly religious family-centric societies: a Focus group study of Indonesian cancer-care professionals.

BACKGROUND: Most studies on advance care planning in Asia originate in high-income Asian countries. Indonesia is a middle-income Asian country characterized by its religious devoutness and strong family ties. This study aims to explore the perspectives and experiences of Indonesian healthcare professionals on advance care planning for cancer patients. METHODS: Focus-group discussions were conducted in July and August 2019 and were analysed using thematic content analysis enhanced by dual coding and exploration of divergent views. Purposive sampling of physicians and nurses actively engaged in cancer care in a national cancer centre and a national general hospital. RESULTS: We included 16 physicians and 16 nurses. These participants were open to the idea of advance care planning. We further identified four aspects of this planning that the participants considered to be important: 1) the family's role in medical decision-making; 2) sensitivity to communication norms; 3) patients' and families' religious beliefs regarding the control and sanctity of life; and 4) the availability of a support system for advance care planning (healthcare professionals' education and training, public education, resource allocation, and formal regulation). Participants believed that, although family hierarchical structure and certain religious beliefs may complicate patients' engagement in advance care planning, a considerate approach to involving family and patients' religious perspectives in advance care planning may actually facilitate their engagement in it. CONCLUSION: Indonesian healthcare professionals believed that, for culturally congruent advance care planning in Indonesia, it was essential to respect the cultural aspects of collectivism, communication norms, and patients' religious beliefs.

Prevalence of Anemia and Factors Associated With Handgrip Strength in Indonesian Elderly Population.

INTRODUCTION: Anemia is a common blood disorder in the elderly which is associated with numerous poor medical outcomes. However, there is currently no study that assesses anemia prevalence of the Indonesian elderly population aged ≥60 years old in multiple provinces and analyzes its association with handgrip muscle strength using a large sample size. AIM: We aimed to elucidate the prevalence of anemia and analyze factors associated with handgrip strength in elderly. METHOD: This was a cross-sectional study using data from the Indonesian Family Life Survey-5 (IFLS-5). All participants aged ≥60 years old were included in this study. Exclusion criteria were: (1) respondents who refused to take health measurements (hemoglobin (Hb) level, handgrip strength, weight, stature, and waist circumference); (2) respondents with incomplete or missing data; (3) respondents with history of stroke; and (4) respondents with history of pain, swelling, inflammation, injury, and surgery on one or both hands within the last 6 months. The dependent variable for this study was handgrip strength. Subjects were classified as weak if the handgrip strength was <28 kg for men and <18 kg for women based on classification from the Asian Working Group for Sarcopenia (AWGS) 2019. The independent variables were Hb level, gender, age, body mass index (BMI), waist circumference, smoking history, comorbidities, and current use of drug therapies. Based on WHO standard, male and female participants with Hb less than 13 g/dL and 12 g/dL, respectively, are defined as anemic. Statistical analyses used included correlation, bivariate logistic regression, and multivariate logistic regression. RESULT: A total of 3192 individuals were selected for analysis. Overall, 38.8% of participants had anemia, and the prevalence of anemia increases with age. A total of 56.30% of participants aged  ≥80 years had anemia. There was a positive correlation between Hb level and handgrip strength in the Indonesian elderly population (r: 0.349; p value: <0.001). Multivariate analysis showed that anemia was significantly associated with weak handgrip strength (OR: 1.557; 95% CI: 1.314-1.846; p value: <0.001).  Age ≥ 80 years (OR: 5.234), age 70-79 years (OR: 3.152), low BMI (OR: 1.827), and hypertension (OR: 1.340) were associated with weak handgrip strength in multivariate analysis. CONCLUSION: The prevalence of anemia in the Indonesian elderly was 38.8% and anemia was associated with weak handgrip strength. The association of anemia with weak handgrip strength is more pronounced in males and the elderly aged ≥80 years.

Association of Somatic Gene Mutations with Risk of Transformation into Acute Myeloid Leukemia in Patients with Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVES: we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk. MATERIALS AND METHODS: The protocol for this systematic review and meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) with ID number of CRD42020218581. Systematic literature search was conducted by all authors up to October 2021 on: (1) PubMed, (2) EBSCOhost, (3) Scopus, (4) JSTOR, and (5) grey literatures. Hand-searching for relevant articles was also conducted. The following keywords with their synonyms and combinations using Boolean operators were applied to all database: "myelodysplastic syndrome", SRSF2", "SF3B1", "U2AF1", "ASXL1", "DNMT3A", "TET2", "IDH1", "IDH2", "RUNX1", "acute myeloid leukemia progression", and "leukemia free survival". Outcome was measured using hazard ratio (HR). RESULTS: We identified 14 articles to be used for this systematic review and meta-analysis. There was no statistically significant difference in AML transformation risk between U2AF1 mutant and U2AF1 wildtype MDS patients (HR: 1.41; 95% CI: 0.95-2.07, p=0.08, I2=0%). Pooled HR showed that patients with SRSF2 mutation had higher risk of AML transformation (HR 2.62; 95% CI: 1.54-4.45; p= .0004; I2= 55%). The pooled HR for SF3B1 was 0.48 (95% CI: 0.22-1.06, p=0.07, I2=55%). Mutations of TET2, ASXL1, and EZH2 were not associated with AML transformation. Meanwhile, DNMT3A mutations were associated with AML transformation with pooled HR of 2.73 (95% CI: 1.43-5.21; p= 0.08; I2: 67%). The pooled HR for IDH genes was smaller (HR: 2.92; 95%CI: 1.21-7.06; p=0.02; I2:65%). Patients with RUNX1 mutation were associated with AML transformation (HR: 1.85; 95%CI: 1.11-3.09; p=0.02; I2:38%). CONCLUSION: Based from our analyses, MDS patients with mutations of SRSF2, DNMT3A, IDH, and RUNX1 have higher hazard ratio for AML transformation.

microRNA-221 and tamoxifen resistance in luminal-subtype breast cancer patients: A case-control study.

BACKGROUND: Around 70% of breast cancers (BCs) are estrogen receptor-α (ERα)-positive. Adjuvant endocrine therapy is used to reduce estrogen levels and inhibit signal transduction through the ER. The anti-estrogen drugs that are most commonly used in endocrine therapy belong to the selective ER modulator (SERM) class and include tamoxifen. Although it has been used for three decades in cases of early-stage and ERα-positive BC, resistance to tamoxifen is a common problem. microRNAs (miRNAs) have a potential role in demonstrating BC resistance to tamoxifen therapy. Hence, there is a need to investigate the expression of miRNA-221 (miR-221) in luminal-subtype BC patients receiving tamoxifen therapy. METHODS: This case-control study investigated luminal-subtype BC patients who had undergone endocrine therapy for at least 1 year. The case group comprised patients with local or metastatic recurrence, and the control group comprised patients without local or metastatic recurrence. RESULTS: There was a significant difference in miR-221 expression (p = 0.005) between the case and control groups. There were no significant differences between the groups that were positive and negative for the progesterone receptor (PR) (p = 0.25), had high and low marker of proliferation Ki-67 levels (p = 0.60), were positive and negative for lymphovascular invasion (p = 0.14), and had stage 2 and stage 3 cancer (p = 0.25). CONCLUSION: miR-221 expression was higher in tamoxifen-resistant BC cases. miR-221 is a potential biomarker of tamoxifen resistance.

Comparison of early mortality between leukapheresis and non-leukapheresis in adult acute myeloid leukemia patients with hyperleukocytosis: a systematic review and meta-analysis.

OBJECTIVES: One of the treatment modalities that can be used for hyperleukocytosis is leukapheresis. However, the result of studies showing the benefit of early mortality through the use of leukapheresis versus no leukapheresis is still inconclusive. Hence, we aimed to conduct a systematic review with meta-analysis to determine the effect of leukapheresis on early mortality in AML patients with hyperleukocytosis. METHODS: We conducted a literature search on five databases (PubMed, EBSCOhost, Scopus, Clinicalkey, and JSTOR) up to October 2021 for studies comparing early mortality outcomes between hyperleukocytosis AML patients treated with leukapheresis versus no leukapheresis. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity tests were presented in I2 value and publication bias was analyzed using a funnel plot. RESULTS: Eleven retrospective cohort studies were eligible based on the inclusion and exclusion criteria. Pooled analysis showed that there was no significant difference in early mortality between patients receiving leukapheresis and not receiving leukapheresis in studies using hyperleukocytosis cutoff of 95,000/mm3 or 100,000/mm3 (OR: 1.17; 95% CI: 0.74-1.86; p: 0.50; I2: 0%). Similarly, studies using hyperleukocytosis cutoff of 50,000/mm3 also showed no benefits of early mortality (OR: 0.67; 95% CI: 0.43-1.05; p: 0.08; I2: 0%). Most of the studies used had a moderate risk of bias due to being observational studies. Funnel plot showed an indication of publication bias on studies using hyperleukocytosis cutoff of ≥50,000/mm3. CONCLUSION: The use of leukapheresis does not provide early mortality benefit in adult AML patients with hyperleukocytosis.

Oxidative Stress (Malondialdehyde) in Adults Beta-Thalassemia Major and Intermedia: Comparison Between Before and After Blood Transfusion and Its Correlation with Iron Overload.

BACKGROUND: Iron overload is a major problem in both transfusion-dependent (TDT) and non-transfusion-dependent thalassemia (NTDT). It has been known to increase oxidative stress. Meanwhile, blood transfusion as main therapy for thalassemia increases iron overload. One of the markers of oxidative stress is malondialdehyde (MDA). This study aims to provide data on MDA levels in adult thalassemia patients, and to compare the levels before and after transfusion in patients with TDT and NTDT. METHODS: This is a cross-sectional, pre-post study in adult patients with thalassemia major and intermedia that received blood transfusion with or without iron-chelating agents in Cipto Mangunkusumo Hospital. Blood samples were taken immediately before the transfusion and one day after. Serum ferritin (SF) assays were conducted by electrochemiluminescence immunoassay method, while transferrin saturation (TS) was calculated by dividing serum iron by the binding capacity. Subsequently, plasma MDA levels assays were performed using the Wills method, and data analysis was conducted using the t-test/Mann-Whitney and Pearson/Spearman correlation test, depending on the data distribution. RESULTS: The 63 respondents recruited consist of 51 TDT and 12 NTDT patients, and their median plasma MDA level before and after transfusion was 0.49 µmol/L and 0.45 µmol/L, respectively. Before transfusion, there was no correlation between SF and MDA, and TS and MDA levels. After the transfusion, there was no correlation between, SF and MDA, or TS and MDA levels. CONCLUSION: There is no significant difference in MDA levels before and after transfusion. Although blood transfusion increases the iron load in thalassemia patients, there was no increase in median MDA level after transfusion. Meanwhile, there was no correlation between markers of iron overload and MDA level in thalassemia patients both before and after transfusion.

The Association Between Triglyceride-Glucose Index as a Marker of Insulin Resistance and the Risk of Breast Cancer.

Background: This study aims to evaluate the association and dose-response between triglyceride-glucose (TyG) index and breast cancer. Method: This is a multicenter case-control study conducted in six public referral hospitals in Indonesia. Cases are individuals aged 19 years or above who were diagnosed with breast cancer within 1 year of diagnosis, based on histopathology and immunohistochemistry. Controls were recruited from corresponding hospitals. TyG index was determined by the formula: ln (fasting TG [mg/dl] × fasting glucose [mg/dl]). Results: There were 212 participants in the breast cancer group and 212 participants in the control group. TyG index was higher in patients with breast cancer (median 8.65 [7.38, 10.9] vs. 8.30 [7.09, 10.84], p < 0.001). When compared with TyG quartile of Q1, Q4 was associated with an OR of 2.42 (1.77, 3.31), p < 0.001, Q3 was associated with an OR of 1.53 (1.21, 1.93), p < 0.001, Q2 was associated with an OR of 1.39 (1.12, 1.73), p = 0.002 for the risk of breast cancer. The dose-response relationship was nonlinear (p < 0.001). On univariate analysis, smoking (OR 2.15 [1.44, 3.22], p < 0.001), use of contraception (1.73 [1.15, 2.60], p = 0.008), alcohol consumption (OR 2.04 [0.96, 4.35], p = 0.064), and TyG Index >8.87 (OR 3.08 [1.93, 4.93], p < 0.001) were associated with risk of breast cancer. Independently associated with increased risk of breast cancer included smoking (OR 1.93 [1.23, 3.01], p = 0.004), use of contraception (OR 1.59 [1.02, 2.48], p = 0.039), and TyG Index >8.87 (OR 2.93 [1.72, 4.98], p < 0.001). Conclusion: TyG index was associated with breast cancer in a nonlinear dose-response fashion.

Repurposing FIB-4 index as a predictor of mortality in patients with hematological malignancies and COVID-19.

BACKGROUND: In this study, we aimed to investigate whether FIB-4 index is useful in predicting mortality in patients with concurrent hematological malignancies and COVID-19. We also aimed to determine the optimal cut-off point for the prediction. METHODS: This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia. Consecutive sampling of adults with hematological malignancies and COVID-19 was performed between May 2020 and January 2021. COVID-19 screening test using the reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal samples were performed prior to hospitalization for chemotherapy. FIB-4 index is derived from [age (years) × AST (IU/L)]/[platelet count (109/L) × âˆšALT (U/L)]. The primary outcome of this study is mortality, defined as clinically validated death/non-survivor during a 3-months (90 days) follow-up. RESULTS: There were a total of 70 patients with hematological malignancies and COVID-19 in this study. Median FIB-4 Index was higher in non-survivors (13.1 vs 1.02, p<0.001). FIB-4 index above 3.85 has a sensitivity of 79%, specificity of 84%, PLR of 5.27, and NLR of 0.32. The AUC was 0.849 95% CI 0.735-0.962, p<0.001. This cut-off point was associated with OR of 16.70 95% CI 4.07-66.67, p<0.001. In this study, a FIB-4 >3.85 confers to 80% posterior probability of mortality and FIB-4 <3.85 to 19% probability. FIB-4 >3.85 was associated with shorter time-to-mortality (HR 9.10 95% CI 2.99-27.65, p<0.001). Multivariate analysis indicated that FIB-4 >3.85 (HR 4.09 95% CI 1.32-12.70, p = 0.015) and CRP> 71.57 mg/L (HR 3.36 95% CI 1.08-10.50, p = 0.037) were independently associated with shorter time-to-mortality. CONCLUSION: This study indicates that a FIB-4 index >3.85 was independent predictor of mortality in patients with hematological malignancies and COVID-19 infection.